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    The EU Clinical Trials Register currently displays   43801   clinical trials with a EudraCT protocol, of which   7264   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2016-004558-13
    Sponsor's Protocol Code Number:Z7224L02
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2020-04-09
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGermany - BfArM
    A.2EudraCT number2016-004558-13
    A.3Full title of the trial
    A double-blind, placebo controlled, multicentre, clinical trial to investigate the efficacy and safety of 12 months of therapy with inhaled colistimethate sodium in the treatment of subjects with non-cystic fibrosis bronchiectasis chronically infected with Pseudomonas aeruginosa (P. aeruginosa)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A double-blind, placebo controlled, multicentre, clinical trial to investigate the efficacy and safety of 12 months of therapy with inhaled colistimethate sodium in the treatment of subjects with non-cystic fibrosis bronchiectasis chronically infected with Pseudomonas aeruginosa (P. aeruginosa)
    A.3.2Name or abbreviated title of the trial where available
    PROMIS II
    A.4.1Sponsor's protocol code numberZ7224L02
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorZambon S.p.A.
    B.1.3.4CountryItaly
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportZambon SpA
    B.4.2CountryItaly
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationZambon S.p.A.
    B.5.2Functional name of contact pointDearbhla Hull
    B.5.3 Address:
    B.5.3.1Street AddressVia Lillo del Duca, 10
    B.5.3.2Town/ cityMilan
    B.5.3.3Post code20091
    B.5.3.4CountryItaly
    B.5.4Telephone number+441243859016
    B.5.6E-mailclinicaltrials@zambongroup.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Promixin, 1 million International Units (IU) Powder for Nebuliser Solution
    D.2.1.1.2Name of the Marketing Authorisation holderZambon S.p.A.
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameColistimethate sodium
    D.3.4Pharmaceutical form Powder for nebuliser solution
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCOLISTIMETHATE SODIUM
    D.3.9.1CAS number 8068-28-8
    D.3.9.3Other descriptive nameColistimethate Sodium
    D.3.9.4EV Substance CodeSUB06801MIG
    D.3.10 Strength
    D.3.10.1Concentration unit IU international unit(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1000000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboNebuliser solution
    D.8.4Route of administration of the placeboInhalation use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Non-cystic fibrosis bronchiectasis chronically infected with Pseudomonas aeruginosa
    E.1.1.1Medical condition in easily understood language
    Non-cystic fibrosis bronchiectasis chronically infected with Pseudomonas aeruginosa
    E.1.1.2Therapeutic area Diseases [C] - Bacterial Infections and Mycoses [C01]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10006445
    E.1.2Term Bronchiectasis
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of the trial is to investigate the effect of the use of inhaled colistimethate sodium, administered twice daily via the I-neb for 12 months, compared to placebo in subjects with NCFB chronically infected with P. aeruginosa on the frequency of pulmonary exacerbations.
    E.2.2Secondary objectives of the trial
    The secondary objectives are to investigate the effect of the use of inhaled colistimethate sodium, administered twice daily via the I-neb for 12 months compared to placebo in subjects with NCFB chronically infected with P. aeruginosa, on:
    - the time to the first pulmonary exacerbation
    - the number of exacerbation-free days
    - the severity of pulmonary exacerbations
    - the time to the first severe pulmonary exacerbation
    - the Quality of Life
    - the pharmaco-economic effect
    - the density and susceptibility of P. aeruginosa and to investigate the emergence of other bacterial colonies and any developing resistance
    - the safety and tolerability of inhaled colistimethate sodium
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Additional plasma samples will be collected from patients at selected
    sites for determination of plasma concentrations of polymyxin E1.
    Samples will be collected at Visit 2 (Randomisation), Visit 3 (Day 28),
    and Visit 7 (End of Treatment) and sparse ambient pharmacokinetics will
    be analysed relative to the time of the last IMP administration.
    E.3Principal inclusion criteria
    Subjects can be included in the trial if they meet all the inclusion criteria listed below:
    1) are able and willing to give informed consent, following a detailed explanation of participation in the protocol and signed consent obtained;
    2) are aged 18 years or older of either gender;
    3) are diagnosed with NCFB by CT (or high-resolution CT) as recorded in the subject’s notes and this is their predominant condition being treated;
    4) had at least 2 NCFB pulmonary exacerbations requiring oral or inhaled antibiotics or 1 NCFB pulmonary exacerbation requiring intravenous antibiotics in the 12 months preceding the Screening Visit (Visit 1) and had no NCFB pulmonary exacerbation with or without treatment during the period between Visit 1 and Visit 2;
    5) have a documented history of P. aeruginosa infection;
    6) are clinically stable and have not required a change in pulmonary treatment for at least 30 days before the Screening Visit (Visit 1);
    7) have pre-bronchodilator FEV1 ≥25% of predicted;
    8) had a positive sputum culture for P. aeruginosa from an adequate sample taken at the Screening Visit (Visit 1) or during the screening period.
    E.4Principal exclusion criteria
    Subjects are not eligible for the trial if they meet one or more of the exclusion criteria listed below:
    1) known bronchiectasis as a consequence of cystic fibrosis (CF);
    2) known history of hypogammaglobulinaemia requiring treatment with immunoglobulin, unless fully replaced and considered immuno-competent by the Investigator;
    3) myasthenia gravis or porphyria;
    4) severe cardiovascular disease such as severe uncontrolled hypertension, ischaemic heart disease or cardiac arrhythmia and any other conditions that would confound the evaluation of safety, in the opinion of the Investigator;
    5) had major surgery in the 3 months prior to the Screening Visit (Visit 1) or planned inpatient major surgery during the study period;
    6) receiving treatment for ABPA;
    7) had massive haemoptysis (greater than or equal to 300 mL or requiring blood transfusion) in the preceding 4 weeks before the Screening Visit (Visit 1) or between Visit 1 and Visit 2;
    8) respiratory failure that would compromise patient safety or confound the evaluation of safety or efficacy of the study in the opinion of the Investigator;
    9) current active malignancy, except for basal cell carcinoma or squamous cell carcinoma of the skin without metastases;
    10) taking immunosuppressive medications (such as azathioprine, cyclosporine, tacrolimus, sirolimus, mycophenolate, rituximab), and/or anti-cytokine medications (such as anti-IL-6 and anti-tumour alpha necrosis factor products) in the preceding year before the Screening Visit (Visit 1);
    11) known history of human immunodeficiency virus (HIV);
    12) current treatment for non-tuberculous mycobacterial (NTM) lung disease or tuberculosis;
    13) known or suspected to be allergic or unable to tolerate colistimethate sodium (intravenous or inhaled) or other polymixins, including evidence of bronchial hyper-reactivity following inhaled colistimethate sodium;
    14) treatment with long term (≥ 30 days) prednisone at a dose of greater than 15 mg a day (or equivalent dose of any other corticosteroid) within six months of the Screening Visit (Visit 1);
    15) new maintenance treatment with any oral macrolides (e.g. azithromycin/erythromycin/clarithromycin) within 30 days of the Screening Visit (Visit 1) or started between Visit 1 and Visit 2;
    16) use of any intravenous or intramuscular or oral or inhaled anti-pseudomonal antibiotic (except chronic macrolides with a stable dose) within 30 days prior to the Screening Visit (Visit 1) and between Visit 1 and Visit 2;
    17) pregnant or breast-feeding or plan to become pregnant over the next year or of child-bearing potential and unwilling to use a reliable method of contraception for at least one month before randomisation and throughout their involvement in the trial;
    18) significant abnormality in clinical evaluations and/or laboratory tests (physical examination, vital signs, haematology, clinical chemistry, clinically relevant impaired renal function, defined as serum creatinine levels ≥2.0x upper limit of normal, ECG) endangering the safe participation of the patient in the study at the Screening Visit (Visit 1) and during the study;
    19) participated in another investigational, interventional trial within 30 days prior to the Screening Visit (Visit 1);
    20) in the opinion of the Investigator not suitable for inclusion for whatever reason.
    E.5 End points
    E.5.1Primary end point(s)
    Primary Efficacy Variable
    The primary variable for this trial is the mean annual NCFB pulmonary exacerbation rate
    E.5.1.1Timepoint(s) of evaluation of this end point
    along the study
    E.5.2Secondary end point(s)
    Secondary Efficacy Variables

    1. time (in days) from the first dose of IMP until the first pulmonary exacerbation;
    2. annualised number of pulmonary exacerbation-free days;
    3. number of severe pulmonary exacerbations defined as those requiring intravenous antibiotics and/or hospitalisation;
    4. the time (in days) from the first does of IMP until the first severe pulmonary exacerbation;
    5. QoL as measured by the total scores of the SGRQ and QOL-B questionnaires as well as changes in SGRQ and QOL-B from baseline to each post-baseline visit;
    6. number of days of work absence due to pulmonary exacerbations;
    7. P. aeruginosa density as determined by the mean change in log10 CFU/g sputum from baseline (Visit 2) to Day 28 of treatment (Visit 3) as well as to Visits 5 and 7.

    Safety Variables
    8. the incidence of TEAEs;
    9. absolute changes in percent-predicted FEV1 from baseline to each post-baseline visit;
    10. the number of subjects experiencing bronchospasm clinically or spirometrically determined following IMP administration at the start and end of treatment;
    11. P. aeruginosa resistance to colistin sulfate as determined by in-vitro susceptibility testing on sputum from Screening (Visit 1) to end of treatment (Visit 7) as well as on sputum from Exacerbation Visits and clinic visits due to pneumonia;
    12. emergence of other bacterial colonies and any developing resistance in sputum from Screening (Visit 1) to End of Treatment (Visit 7);
    13. haematology, clinical chemistry and renal function tests;
    14. physical examination and vital signs data;
    15. 12-lead electrocardiogram.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Secondary Efficacy Variables
    1 from first dose until first pulmonary exacerbation
    2 and 3 along the study
    4 from first does until first severe pulmonary exacerbation
    5 from baseline to each post-baseline visit
    6 along the study
    7 from baseline (Visit 2) to Day28 (Visit 3) and to Visits 5 & 7
    Safety Variables
    8 along the study
    9 from baseline to each post-baseline visit
    10 end of treatment
    11 from Screening (Visit 1) to end of treatment (EoT)(Visit 7) and on Exacerbation Visits and visits due to pneumonia
    12 and 13 from Screening (Visit 1) to EoT (Visit 7)
    14 physical examination: at Screening (Visit 1), EoT (Visit 7) and Exacerbation Visits/vital signs: from Screening (Visit 1) to EoT(Visit 7) and on Exacerbation Visits
    15 at Screening (Visit 1) and EoT (Visit 7)
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA45
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    United States
    France
    Poland
    Argentina
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months10
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 210
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 210
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state80
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 112
    F.4.2.2In the whole clinical trial 420
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    After the end of the study the patient will return to standard treatment
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-12-01
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-08-13
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2022-03-15
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